The mechanisms of enzyme induction mediated by 3',5'-cyclic nucleotides are being investigated in an established line of rat hepatoma cells. We have studied the ability of cyclic AMP to increase the rate of synthesis of tyrosine aminotransferase, the effect of cell culture conditions on this response and the possible protein kinases involved. In addition, we have found that the rate of tyrosine aminotransferase degradation is inversely related to the cellular concentration of cyclic GMP. This correlation has been observed in primary cultures of rat hepatocytes, as well as in hepatoma tissue culture cells. We have observed that tyrosine aminotransferase is a poor substrate for cyclic nucleotide-dependent protein kinases, suggesting that a mechanism other than direct phosphorylation of tyrosine aminotransferase itself is involved in the regulation of its degradation. These studies should enhance our understanding of the roles of cyclic nucleotides in regulating the amounts of specific enzymes in normal and neoplastic cells.